A novel role for ADAMTS13 in hyperfibrinolysis after trauma-induced shock☆. Br J Anaesth 2026 Jan;136(1):107-116
Date
10/08/2025Pubmed ID
41058374Pubmed Central ID
PMC13269631DOI
10.1016/j.bja.2025.07.092Scopus ID
2-s2.0-105018014055 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
BACKGROUND: Trauma-induced coagulopathy with hyperfibrinolysis is associated with high mortality. The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs 13) is cleaved after tissue injury. We analysed the underlying mechanism of ADAMTS13 proteolytic cleavage and the effect of ADAMTS13 on trauma-induced hyperfibrinolysis.
METHODS: Thirty-nine trauma patients with shock were stratified based on ADAMTS13 conformation. Mechanisms of ADAMTS13 cleavage were explored in vitro using blood from healthy volunteers. The role of ADAMTS13 in hyperfibrinolysis was examined using rotational thromboelastometry (ROTEM) and a fibrin formation assay.
RESULTS: ADAMTS13 circulated in a truncated and hyperactive form in 23% of trauma patients in shock. Truncated ADAMTS13 was associated with a significant increase in hyperfibrinolysis (ROTEM FIBTEM maximum lysis 85 [62-100] vs 1 [0-7]%, P=0.002) and mortality (44% vs 3%, P=0.007) compared with patients with a closed ADAMTS13 conformation. In vitro, ADAMTS13 was cleaved at its distal self-regulating domains in the presence of tissue plasminogen activator and plasmin, which concentration-dependently increased ADAMTS13 activity. This activation was prevented by tranexamic acid. Hyperactivated ADAMTS13 was associated with hyperfibrinolysis by both ROTEM and fibrin formation assays compared with conditions where ADAMTS13 was inactivated.
CONCLUSIONS: During trauma-induced shock, ADAMTS13 can circulate in a truncated and hyperactivated conformation, which is associated with hyperfibrinolysis and mortality. In vitro, tissue plasminogen activator and plasmin can truncate ADAMTS13, increasing its activity. Additionally, ADAMTS13 directly contributes to hyperfibrinolysis, and tranexamic acid can prevent ADAMTS13 degradation.
INSTITUTIONAL ETHICAL REVIEW BOARD APPROVAL NUMBERS: NL58766.018.16, NL74188.018.20.
Author List
Sloos PH, Vermeersch L, Roozendaal DS, Delmote AS, Veer CV', Momanyi TO, Miranda FZ, Muia J, Tersteeg C, Vanhoorelbeke K, Juffermans NP, Kleinveld DJBAuthor
Joshua Muia PhD Assistant Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ADAMTS13 ProteinAdult
Aged
Blood Coagulation Disorders
Female
Fibrinolysis
Humans
Male
Middle Aged
Shock, Traumatic
Thrombelastography
Tranexamic Acid
Wounds and Injuries
Young Adult
